Surg Oncol Clin N Am

14 (2005) 85–102

Breast cancer treatment in older women

Marissa Howard-McNatt, MDa,
Kevin S. Hughes, MDa,*, Lauren A. Schnaper, MDb,
Julie L. Jones, MDa, Michele Gadd, MDa,
Barbara L. Smith, MD, PhDa
a
Division of Surgical Oncology, Massachusetts General Hospital,
100 Blossom Street, Cox 626, Boston, MA 02114, USA
b
Greater Baltimore Medical Center Comprehensive Breast Care Center, Greater Baltimore
Medical Center, 6701 North Charles Street, Suite 5105, Baltimore, MD 21204, USA

Breast cancer is a substantial problem in elderly women. It was reported

that 30% of all breast cancers occur in women who are older than 70 years
of age and 48% occur in women who are older than 65 years of age [1]. As
the baby boom population ages and the health of older women improves,
the number of women who are older than 65 is predicted to nearly double by
2050. In 1997, the life expectancy was 79.9 years for white women and 74.7
years for black women. The life expectancy for both races from 2001 is
shown in Table 1. In 2025, the projected life expectancy is 84.8 years and
82.7 years for white and black women, respectively [2]. This will increase
markedly the percentage of breast cancers that occur in this age group. This
article discusses the treatment of breast cancer in the elderly and whether
disparities exist in their treatment, quality of life, and survival when
compared with their younger counterpart.
In treating older women, it is important to understand the biology of the
disease, the impact that comorbidities have on survival, and the
psychosocial status of the patient. In general, breast cancer in the elderly
is less aggressive and life expectancy is shorter than in the younger patient.
Life expectancy in older patients can still be substantial—16 years for
a 70-year-old and more than 6 years for a healthy 80-year-old [3]. The goal
of treatment in older patients is control of disease for a finite lifetime rather
than the expectation of cure, as in younger patients who can anticipate
decades of life.

* Corresponding author.
E-mail address: kshughes@partners.org (K.S. Hughes).

1055-3207/05/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.soc.2004.07.006
86 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102

Table 1
Average remaining lifetime at various ages according to race, preliminary data from 2001
Life expectancy
Age (y) White women (y) Black women (y)
60 23.5 21.5
65 19.5 17.9
70 15.7 14.7
75 12.3 11.8
80 9.3 9.2
85 6.7 7.0
90 4.8 5.3
Data from National Vital Statistics Reports 2003;51(5):25.

Yancik et al [4] found that elderly women have equivalent survival when
compared with younger women in terms of localized disease; however,
comorbid disease plays a significant role with regard to actual survival. In
1994, Satariano et al [5] reported that mortality in women who were aged 40 to
54 years at the time of diagnosis was nearly six times more likely to be
attributable to breast cancer than to some other cause. In contrast, mortality
in women who were aged 75 to 84 years at diagnosis was attributable to breast
cancer in fewer than 50% of cases. Overall survival was related directly to the
presence of comorbid conditions (eg, heart disease, diabetes, other cancers,
respiratory illnesses) and was related inversely to patient age. There was a 20-
fold increase in nonbreast cancer deaths in patients who had three or more
comorbid conditions. Furthermore, comorbidity may limit the choice of
therapy. For example, congestive heart failure, which is more common in the
elderly, may limit or preclude the use of doxorubicin-based chemotherapy.
The number of comorbid conditions of the elderly will decline in the
future as a result of better health care and healthy living. These factors will
expand treatment options for the elderly. If warranted by disease
presentation, healthier, older women will be candidates for more aggressive
breast cancer therapy. Older survivors of breast cancer who continue to see
oncologists after treatment tend to receive better secondary prevention and
general medical care than those who do not; this promotes a healthier,
longer survival [6] Thus, in discussing the care of the elderly, physiologic,
rather than chronologic, age must be considered.

Patterns of care
Despite the fact that one third of breast cancer occurs in women who are
older than 70, until recently, they have been excluded from clinical trials [7].
Because there is no database treatment recommendations that specifically
are for the elderly, clinicians are free to individualize care plans based on
extrapolated data and experience. This led to accusations of overtreatment
 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102 87

and undertreatment of older women who had breast cancer. In the past,
more women were treated primarily with mastectomy [8]—possible over-
treatment. Of those who received breast-conserving surgery, many did not
undergo axillary dissection and were not followed by radiation therapy—
possible under treatment [8–10].
Mandelblatt et al [11], in studying patterns of treatment in the elderly,
found that age was a strong determinant of treatment; this confirmed the
existence of age bias among physicians. They also noted that patient
preferences influenced treatment choices. It has long been known that care
patterns vary with geographic location and hospital characteristics. As with
other patients who have breast cancer, older women are more likely to
receive breast-conserving treatment at large urban hospitals or teaching
hospitals that have radiation therapy centers and support services for the
elderly [12].
Velanovich et al [13] pointed out that current local and national
databases that are used to assess outcomes do not reflect the complexity of
issues that are involved when making treatment recommendations to older
women. Information regarding other illnesses and psychosocial influences
are not recorded routinely.
Although it is well-documented that older women receive less therapy, it
is not clear whether this has a negative impact on survival. Because of the
dearth of randomized trials or standardized outcomes research, lesser care
has not been established as detrimental. Although observational studies
linked higher rates of recurrence and decreased survival to undertreatment
[14], Gajdos and coauthors [15] retrospectively studied undertreatment and
standard therapy in elderly patients who had breast cancer and found no
differences in survival.

Biology
Breast cancer in the elderly seems to be less aggressive. Older women tend
to have more estrogen receptor–positive tumors [16], whereas S-phase [17],
grade [18], and p53 and HER2/neu expression [17] are decreased. Older
women tend to have more lobular, mucinous, and papillary cancers than
their younger counterparts [17]. A recent prospective review of 919 patients
who had T1a and T1b tumors identified three factors as independent
predictors of axillary nodal metastases—increasing tumor size (0.1-cm
gradients), poor histologic grade, and younger age [19].
The literature contains conflicting data about the stage at which older
and younger patients present. For example, Barchelli and Balzi [20] found
that in patients who were younger than 39 years old, 59% had nodal
involvement compared with 22% of patients who were older than 80;
however, 43% of the older women did not have pathologic staging of the
axilla. The total number of cases of localized disease that were reported in
88 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102

the Surveillance Epidemiology and End Results program (SEER) database

from 1992 to 1999 showed that 56% of the cases were in women who were
younger than 50 years of age, whereas 66% of the cases were in older
women. Furthermore, regional spread is more common in younger patients
(37%) than in women who are older than 50 (26%) [21]. No clear conclusion
can be drawn about staging in the elderly population.

Psychosocial factors
Younger and older women regard a diagnosis of breast cancer differently.
Breast cancer may be only one of several illnesses in an older patient,
whereas it is more likely to be the only, or one of a few, diseases in a young
woman. As women age, many become more frightened of deteriorating
physical abilities and of dependence on others than of dying.
Overall, elderly patients tend to cope better psychologically with the initial
diagnosis of breast cancer [22,23]. Ganz et al [22] used interview methods to
study quality-of-life issues longitudinally after their breast cancer treatment in
691 women who were older than 65 years of age. They noted a decline in the
functioning levels that began in the 3 months posttreatment and lasted for
the 15 months of the study. Specifically, at 3 months postoperatively they
observed a significant deterioration in self-reported physical functioning that
was associated with the number of comorbid conditions and chemotherapy
but with no other cancer-specific treatments. In the year after breast cancer
surgery, specific breast cancer treatments (mastectomy versus breast
conservation, chemotherapy, or tamoxifen) were not associated with differ-
ences in the quality of life [24]. Psychologic adjustment also can be predicted by
the existence of multiple life stressors before diagnosis, including loss of a child
or spouse or other major life changes [25].
Young women are more likely to explore numerous sources to inform
themselves about the nature of breast cancer and treatment options. They
seek advice from physicians, but they also tend to use such tools as the
Internet—be it good or bad—to gather additional, and sometimes,
confusing, information.
Older patients tend to rely on the advice of their physicians. Petrisek and
his colleagues [26] found that the elderly are less likely to want to be
involved in decision-making about treatment options and are less likely to
seek second opinions. Other studies showed that physicians tend to spend
more time with, and provide more information to, younger patients [27,28].
Maly et al [29], in a study that involved retrospective patient reporting,
found that older women who had breast cancer received much less
informational support than their younger counterparts, although their
informational requirements were seen as similar. Some older women may
find it difficult to understand the complexities of the disease and the
treatment options. The physician must lend a more sympathetic ear to these
individuals and patiently explain all aspects of the disease, prognosis, and
 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102 89

treatment options. It is unclear whether the apparent age-related differences

in patient participation in the decision process are due to generational
differences, physician bias, or decreased ability to process information.
Perhaps as baby boomers mature, they will continue to be more informed
consumers then were previous generations.
A sense of autonomy and good cosmetic outcome are probably as
important to older women as they are to the younger patient. One study
found that most women who were older than 70 years of age wanted breast
conservation therapy and were prepared to go through radiation treatments,
if needed, to preserve their breasts [30].
In dealing with the elderly, it is vital to consider quality of life. These
issues include independent living, social support, ability to perform activities
of daily living, religious commitments, transportation, and attitudes
concerning death. Such concerns strongly influence the patient’s treatment
choices and their ability to follow through with the demands of therapy.

Screening
The risk of developing breast cancer increases with age; therefore, older
women benefit from breast cancer screening, including mammograms,
clinical breast examination, and breast self-examinations. A large meta-
analysis of screening mammography showed that routine annual or biennial
mammography in women who were age 50 to 75 years was associated with
a reduction in breast cancer–related mortality of 25% to 30% within 5 to
6 years of initiation [31]. Mammograms in the older population tend to be
easier to read because of the involution of breast tissue and increase in the
fat content. In addition, the longer doubling time of cancer in older women
increases the window of opportunity for detecting cancer at an earlier stage.
Faulk and his colleagues [32] compared mammographic results of women
who were aged 50 to 64 years (n = 21,226) with those who were aged
65 years and older (n = 10,914). They found that mammography had a
higher predictive value, a higher yield of positive biopsies, and a greater
cancer detection rate per 1000 studies in older women. Despite the useful-
ness of imaging in older women, many do not obtain annual mammograms.
Van Harrison and colleagues [33] reviewed mammography use rates in older
women who were covered by Medicare over a 5-year period between 1993
and 1997. In their sample of 10,000 women, 43% did not have a mammo-
gram at all, whereas the other 57% only had a mean of 2.8 mammograms
during the 5-year study period.
How long should elderly patients continue to receive mammograms?
There is no proof that screening improves survival in women who are older
than 75; however, women should be screened based on their functional
status and biologic age. Some experts recommend mammography for
healthy women up to the age of 85 years [34]. Mandelblatt and colleagues
[35] found that the benefits of screening mammography outweighed the
90 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102

financial costs for older women, irrespective of age; however, the magnitude
of benefit decreased with increasing age and increasing comorbidity when
compared with physical examination. Singletary et al [36] found that most
tumors that were detected on breast self-examination by women who were
older than 69 years of age were T2 to T4 at presentation in comparison with
occult tumors that were detected by mammography in younger women. The
American Geriatrics Society Clinical Practice Committee recommends
annual or biennial mammography until age 75 and then biennially or every
3 years thereafter in women who have a life expectancy of 4 or more years
(Table 2) [37].
The decrease in mammography rates in the elderly is attributable to poor
level of function, limitations in activities of daily living, low income, fewer
primary care visits, and failure of physicians to recommend or discuss
mammography. Attention to reversing these factors improves screening
rates [38–41]. The physician’s recommendation, however, is probably the
most important stimulus for obtaining screening mammography in older
women [42].
In our practice, we tend to recommend mammography for as long as the
woman can come in easily for the study. Although this may not increase
survival, we believe that it allows us to find smaller cancers that are treated
more easily.

Treatment
As with all malignancies, recommendations for primary treatment of
breast cancer should be based on stage at presentation. In a cohort of older
women in the United Kingdom, Golledge et al [43] found that women who
were older than 70 presented more frequently with T3 and T4 tumors,
although the rate of axillary lymph node involvement was similar to that of
younger women. Alternatively, Greenfield and coauthors [44], in a 1987
retrospective chart review from UCLA, noted that women who were older
than 70 had more stage 1 and stage 2 tumors at diagnosis when compared
with women who were 50 to 69 years of age (87% and 81%, retrospectively).

Table 2
Breast cancer screening recommendations for older women (ref. 22)
Screening modality Recommendation
Mammography Annual or biennial mammography until age 75
and biennial or every 3 years thereafter, with
no upper age limit for women with an estimated
life expectancy of 4 or more years.
Clinical breast examination Annual
Breast self-examination Monthly
Data from American Geriatrics Society Clinical Practice Committee. AGS Position
Statement: breast cancer screening in older women. J Am Geriatr Soc 2000;48:842–4.
 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102 91

The National Adjuvant Breast and Bowel Project (NASBP) Protocol

B-06 showed that invasive breast cancer could be treated by modified radical
mastectomy or by lumpectomy, axillary dissection, and breast radiation [45].
At 26 years of follow-up there was no difference in survival between the two
groups [46]. In many cases, elective sentinel lymph node biopsy can be an
alternative to axillary dissection [47]. When given a choice, women who are
aged 70 and older are more likely to choose breast-conserving surgery than
mastectomy [31]. Older women should be offered the option of breast
preservation, because body image and the loss of a breast is an important
issue, regardless of age.
Older patients consistently receive standard breast cancer treatments less
frequently than younger patients, even when controlling for comorbidity,
cognitive status, and functional status. Yancik et al [4] found that surgery
was performed less frequently in women who were older than 85 years than
in younger women. Bergman et al [48] found that older women had less
extensive surgical procedures and less adjuvant radiation. The decreased use
of radiation or surgery may be interpreted as substandard care or as
appropriate care, depending on the characteristics of the patient and of the
tumor.
Most elderly patients can undergo surgery with minimal morbidity.
Operative mortality rates for mastectomy that is performed under general
anesthesia are approximately 1% [49,50]. Although surgery and anesthesia
are not risk-free, the main factor that influences surgical morbidity is
comorbidity [48]. The complication rate in women who are older than 65 is
reported to be low and usually is related to local wound problems [51].
Short-term decrease in cognitive function after general anesthesia in the
elderly also was documented [52].
Older women tolerate breast irradiation as well as younger women [53];
however, elderly patients may find that 6 weeks of radiation therapy is
exhausting and may have difficulty arranging transportation. The Milan 3
Trial found that in women who were treated with quadrantectomy without
breast irradiation, those who were younger than 45 years of age had an
ipsilateral breast tumor recurrence rate of 17.5%, compared with a rate of
3.8% in women who were older than 55 [54]. More importantly, it is not
proven that local recurrence influences survival greatly.
Standard treatment for breast cancer has similar disease-free and overall
survival rates in older and younger women; however, older women have
more deaths from nonbreast cancer illness (11% versus 2%; P = .0006)
[55,56].

Management of the axilla

Axillary dissection is used to stage the disease, to help make treatment
decisions, to gain prognostic information, and to prevent axillary
92 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102

recurrence. For patients who have small estrogen or progesterone (ER/PR)

receptor–positive tumors in whom chemotherapy is unlikely to be used, it
may be reasonable to exclude axillary evaluation and to treat the patient
with lumpectomy, radiation, and tamoxifen. One retrospective study of
elderly patients, aged 70 to 92 years, who were treated with lumpectomy plus
tamoxifen but without radiation or axillary dissection, showed that at 5 and
10 years after initial surgery, relapse rates in the ipsilateral axilla were 4.3%
and 5.9%, respectively [57]. Cancer and Leukemia Group B (CALGB)
performed a randomized clinical trial for women 70 and over who had
T1-clinical N0M0 ER/PR–positive breast cancer [58]. All participants were
treated with lumpectomy plus tamoxifen and were randomized to receive
breast radiation or no further treatment. At a median of 5 years of follow-
up, none of the 200 women who received radiation therapy plus tamoxifen,
but no axillary dissection, had axillary recurrences. Of the 204 who had
lumpectomy plus tamoxifen but no axillary dissection, two patients (1%)
had an axillary recurrence. Accordingly, axillary recurrence is rare in older
women who have favorable ER-positive tumors with or without radiation.
Axillary lymph node dissection can be associated with significant
posttreatment morbidity, including lymphedema, pain, and decreased upper
extremity range of motion [59,60]. Complications that involve decreased use
of an upper extremity can be especially debilitating in the elderly who often
are teetering on the edge of being unable to care for themselves.
There are, of course, some patients in whom axillary treatment or
evaluation is necessary. In women who have large tumors, ER/PR-negative
markers, or clinically-positive axillary nodes, axillary dissection represents
the most effective method to decrease local recurrence and to obtain useful
treatment information. Sentinel lymph node mapping, which identifies the
first node that drains the breast, may prove to be an accurate and preferable
alternative to axillary dissection in older patients.

Radiation therapy
Should radiation therapy be used after breast-conserving surgery in the
elderly? Radiation therapy has been shown repeatedly to reduce the rate of
local recurrence in all age groups. Recently, the Early Breast Cancer
Trialists’ Collaborative Group (EBCTG) showed in a meta-analysis that
ipsilateral breast tumor recurred in 27.2% of patients who did not receive
radiation therapy after breast conservation [61]. Those who underwent
breast irradiation had a local recurrence of 8.8% (P \ .00001). The EBCTG
overview analysis did not show a survival advantage for radiation therapy.
At 20 years of follow-up, the decrease in cancer-related deaths in patients
who underwent radiation was offset by mortality from other causes [61].
Although the elderly are able to tolerate radiation treatments as well as their
younger counterparts [62,63], some investigators suggest that the schedule
 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102 93

and duration of adjuvant breast radiation may be an obstacle for older

patients. Sandison et al [29] found that only one of 31 patients who was
offered radiation refused secondary to scheduling problems.
Short- and long-term morbidity, including chest wall pain, rib fracture,
pneumonitis, and fibrosis are associated with radiation therapy [59,60].
These can be especially problematic in patients who are elderly or ill.
Some patients are too debilitated to undergo radiation treatments. In
such patients, the addition of radiation therapy has little survival benefit
over surgery alone. Shorter life expectancy, especially in women who have
comorbid conditions, translates into a decreased length of time in which an
elderly patient is at risk for recurrence. In patients who have ipsilateral
recurrence and who did not receive radiation, re-excision and radiation are
an option. Liljegren et al [64] reported that 11 of 37 (30%) patients who had
ipsilateral breast cancer recurrence were able to undergo repeat wide
excision plus radiation. Conservative salvage treatment also was reported in
18 out of 28 (64%) patients by Veronesi [54] and in 43% of patients (46 of
108) by Clark et al [65].
Tamoxifen has been suggested as a substitute for radiation to decrease
local recurrence in subsets of women who have favorable tumors. NASBP
B-21, a prospective trial, randomized 1009 women who had ER-positive
cancers that were up to 1 cm in diameter to tamoxifen alone, tamoxifen plus
radiation, and radiation plus placebo. Cumulative incidence of ipsilateral
breast tumor recurrence was 16.5% with tamoxifen alone, 9.3% with
radiation, and 2.8% with tamoxifen plus radiation [66]. When women who
were 70 years of age or older were examined, the ipsilateral breast cancer
recurrence rate was 1.3% per year in those who were randomized to
tamoxifen alone, regardless of ER status [67]. Preliminary data from Hughes
et al [58] also showed that women who were 70 years of age and older who
were treated with wide excision and tamoxifen alone had a 1.3% recurrence
rate at 28 months.

Tamoxifen and aromatase inhibitors to prevent distant metastasis

Aside from its effect on Ipsilateral Breast Tumor Recurrence (IBTR),
tamoxifen is useful for decreasing distant metastasis and increasing survival.
A study from the Eastern Cooperative Oncology Group randomized women
who were aged 65 to 84 years and had node-positive breast cancer to 2 years
of tamoxifen or placebo [68]. The median time to recurrence was 4.4 years
with placebo and 7.4 years with tamoxifen. At 2 years, the survival between
the two groups was the same.
NASBP Protocol B-14 showed a significant increase in disease-free
survival in postmenopausal women who were node-negative and receptor-
positive that were subsequently treated with tamoxifen [69]. The EBCTG
overview of tamoxifen trials also concluded that patients who are estrogen-
receptor positive receive a significant benefit from the addition of tamoxifen
94 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102

[70]. With the use of adjuvant tamoxifen for 5 years, the proportional
reduction in recurrence during approximately 10 years of follow-up was
47%, whereas the proportional reduction in mortality was 26%. The
absolute improvement in 10-year survival was 10.9% for patients who were
node positive (61.4% versus 50.5%, P \ .00001) and 5.6% for patients who
were node negative (78.9% versus 73.3%, P \ .0001) patients. There was
a 47% decrease in the rate of contralateral breast cancer. Based on these and
other studies, the use of tamoxifen in older women has become standard
therapy, although no trials have measured efficacy directly in this age group.
Overall, in women who are 70 years of age or older and have ER-positive
tumors, tamoxifen seems to have substantial benefit with minimal risk. This
is especially true in patients who undergo breast conservation; tamoxifen
decreases the risks of ipsilateral and contralateral breast cancer and the risk
of distant recurrence.
Postmenopausal women can now consider the use of aromatase
inhibitors (AIs) as an alternative or follow-up treatment to tamoxifen.
These drugs include anastrozole, letrozole, and exemestane. AIs function by
suppressing endogenous estrogens to extremely low levels. The Arimidex,
Tamoxifen, Alone or in Combination (ATAC) trial, a randomized trial in
postmenopausal women who had operable breast cancer, showed in its first
analysis that the use of anastrozole resulted in a longer, distant disease–free
survival and time-to-recurrence than tamoxifen [71]. In the recent ATAC
trial efficacy and safety update, anastrozole continued to show improved
disease-free survival (86.9% to 84.5%, P = .03) and increased time-to-
recurrence (P = .015), especially in hormone receptor–positive cancers [72].
Furthermore, the study by Goss and colleagues [73] showed that women
who had completed 5 years of tamoxifen, when randomized to letrozole
versus placebo, had estimated 4-year disease-free survival rates of 93% and
87%, respectively (P \ .001). These data suggest that AIs may be more
effective than tamoxifen and, with confirmatory studies, may become the
adjuvant endocrine therapy of choice [74].

Endocrine therapy alone as treatment

Originally, the use of tamoxifen alone for initial treatment of localized
breast cancer was studied in women who were not candidates for surgery. In
a study by Preece et al [75], 67 women who were aged 75 years and older
who had clinically-localized breast cancer were treated with tamoxifen
alone, without surgery. Seventy-three percent responded to treatment. Five-
year survival was 49.4% and was greatest for those who showed an initial
complete response.
Other studies found that up to 63% of patients who were treated with
tamoxifen alone as a first-line treatment had tumor regression [76]. The
median time of response to tamoxifen was 13.5 weeks and tumor regression
 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102 95

persisted for up to 5 years in one third of patients; however, high relapse

rates, that often required additional local treatment were found during
follow-up [77].
AIs also may have a role in definitive therapy in older, frail patients. In
a recent nonrandomized trial, the preoperative use of exemestane, an AI,
showed greater reduction in tumors that were larger than 3 cm than was
noted previously with tamoxifen [78]; however, in another small, random-
ized study of tamoxifen versus letrozole, there was no difference in tumor
regression [79]. Endocrine therapy as primary treatment is of value only in
women who have receptor-positive breast cancer whose coexisting illnesses
render them unable to tolerate surgery or in those who refuse surgical
treatment.
Recently, AIs have been proposed as preoperative therapy in older
patients. Eiermann and his colleagues performed a randomized, prospective
trial comparing letrozole and tamoxifen in postmenopausal women with ER
and/or PR-positive breast cancers who were not candidates for breast
conservation [80]. The overall response rate assessed by clinical examination
was higher in the letrozole group (55%) when compared to tamoxifen (36%)
(P \ .001). Furthermore, in a small study by Miller and Dixon [78], 8 out of
10 patients who would have required mastectomy before treatment with an
AI were able to undergo breast-conserving surgery. AIs play a role in
making breast-conserving surgery feasible.

Chemotherapy
The use of adjuvant chemotherapy in the elderly has not been studied
directly. Chemotherapy is underused in older women, despite the fact that
treatment of locally advanced and metastatic disease indicates that the
elderly can tolerate treatment [9,81,82]. Age is an independent predictor of
physician recommendation for cytotoxic therapies; however, older age does
not seem to influence patient acceptance of treatment recommendations
[83,84]. The meta-analysis by the EBCTG looked at the effect of age on
results of adjuvant chemotherapy [85]. Use of chemotherapy resulted in
a 10% reduction in death from breast cancer in women who were 60 to 69
years of age. Because there was a small numbers of participants who were
older than 70, there was no discussion of the results in this age group.
Women who up to 40 years of age had a 37% reduction in recurrence and
a 28% reduction in deaths from breast cancer, whereas women who were
between 20 and 69 years of age had an 18% reduction in recurrence and
a 9% reduction in deaths from breast cancer. Recently, the International
Breast Cancer Study Group compared cyclophosphamide, methotrexate,
and 5-Fluorouracil (5-FU) (CMF) with tamoxifen [86]. They found a 15%
survival advantage with chemotherapy in patients who were between 60 and
80 years of age and had ER-negative tumors. In contrast, the group that had
ER-positive tumors obtained no benefit from combination treatment.
96 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102

Chemotherapy regimens may need to be tailored to the older patient.

When standard-dosage CMF chemotherapy is used in patients who are
between 65 and 90 years of age for the treatment of advanced breast cancer,
toxicity is increased. If dosages are decreased to complement creatinine
clearances, toxicity levels are similar to those in younger patients but
response rates may diminish [87]. Older patients must be assessed for
adriamycin tolerance and should have an adequate life expectancy to receive
treatment-based mortality advantages. Chemotherapy may be most
beneficial for patients who have ER-negative tumors and few comorbid
conditions.

Summary of management
Screening
Annual clinical breast examination and monthly breast self-examination
are recommended for all women. Annual mammography is recommended
up to 75 years and should be continued after age 75 in women who have few
limiting comorbid conditions and reasonable life expectancy. Compliance
with mammography is best if recommended by the primary care physician.

Local definitive therapy

There is no universal approach for managing the primary tumor in older
women who have breast cancer. Recommendations must be individualized
to the patient and the tumor presentation. Table 3 gives a synopsis for the
treatment of a primary breast cancer.
Healthy women who present with large, ER-positive tumors that cannot
be treated with breast conservation can be given preoperative hormonal
therapy in an attempt to convert to breast-conserving surgery or can
undergo a simple mastectomy with sentinel node biopsy. Healthy patients
who have large, ER-positive tumors and clinically-positive axillary nodes
also can be given preoperative hormonal therapy to try to convert to
conservation or can have a modified radical mastectomy. Healthy women
who present with large, ER-negative tumors that cannot be treated with
breast conservation should undergo a simple mastectomy with sentinel node
biopsy.
Candidates for breast conservation include patients who have small
tumors relative to breast size. Those who are surgical candidates and have
clinically-positive nodes are treated best by lumpectomy and axillary node
dissection followed by breast radiation. Those who have clinically-negative
nodes and ER/PR-negative tumors or who have a high probability of
positive nodes and who are potential candidates for adjuvant postoperative
chemotherapy should be considered for lumpectomy and sentinel lymph
node biopsy followed by radiation.
 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102 97

Table 3
Treatment recommendations for management of a primary breast cancer
Conservation ER/PR Clinical Health Suggested
possible status node status statusa treatment
No Positive Negative Poor Tamoxifen or an aromatase
inhibitor
No Positive Positive Poor Tamoxifen or an aromatase
inhibitor
No Positive Negative Good Preoperative
hormonal therapy to try
to convert to conservation
or simple mastectomy with
sentinel node biopsy
No Positive Positive Good Preoperative hormonal
therapy to try to convert
to conservation or modified
radical mastectomy
No Negative Negative Good Simple mastectomy with
sentinel node biopsy
No Negative Positive Good Modified radical mastectomy
Yes Positive Negative Good Lumpectomy with or without
sentinel node biopsy
Yes Negative Negative Good Lumpectomy with sentinel
node biopsy
Yes Positive Positive Poor Tamoxifen or an aromatase
inhibitor
Yes Positive Positive Good Lumpectomy and axillary
dissection
a
Poor health means limited life expectancy.

Primary hormonal therapy (tamoxifen or an AI) can be used in patients

who have large or small ER- or PR-positive tumors who are too frail to have
surgery or have limited life expectancy. Some patients are not surgical
candidates and have ER-negative tumors. Individualized treatment and
open discussions with the patient and family are essential.

Systemic adjuvant therapy

Adjuvant hormonal therapy should be considered in all postmenopausal
women who have hormone receptor–positive tumors. Tamoxifen has been
the standard hormonal therapy for postmenopausal women. There is
increasing use of AIs as second-line therapy after relapse on tamoxifen or as
primary therapy in women who have contraindications to tamoxifen (eg,
history of endometrial malignancy or thromboembolic events). Only older
women who have an extremely low risk of distant metastases or severe
comorbid illness should not be offered endocrine therapy. Adjuvant
chemotherapy should be considered for older women whose risk of systemic
recurrence is high and who are in good health and have an estimated
98 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85–102

survival of at least 5 years. Chemotherapy is most beneficial in older women

who have ER-negative tumors that exceed 2 cm and have negative lymph
nodes or tumors of any size that have significant nodal involvement. For
older women who have ER-positive or PR-positive tumors, there only is
a small benefit of chemotherapy over tamoxifen alone, even in those who
have positive lymph nodes.
The authors recommend radiation therapy after breast-conserving
surgery to patients who have tumors that are larger than 2 cm, regardless
of ER status. In patients who are taking tamoxifen and have small (\2 cm)
tumors that are ER-positive and clinically node-negative, radiation may not
be needed. It is hoped that the results of CALGB 9343 will shed some light
on this issue.

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